Affected family of the mother.
1.
Molecular and hormonal study.
The hormonal study of the aunt and the mother of the proband (subjects II.
2 and II.
3) included an ACTH test, whose baseline and stimulated levels of 170H Progesterone were normal, not allowing to clarify whether these subjects were heterozygous for a CYP21A2 mutation.
The molecular study was performed on genomic DNA extracted from leukocytes and the seven most frequent mutations of the CYP21A2 gene were studied with allele-specific PCR (Fardella, 1998).
This study demonstrated in the paternal family (subjects II.2, II.4, II.6) the Q318X mutation in exon 8, which consists of changing a glutamine by a stop codon.
This result did not allow classifying the maternal family and therefore deciding on the need for prenatal treatment in these couples.
Subsequently, the CYP21A2 gene was sequenced at the University of São Paulo according to the classical techniques (Wedell, 1993).
Using this methodology, one of the alleles of the paternal family (subjects II.2, II.4, II.6) was found to be the mutation Q318X together with the mutation R483G> trypphan.
In the maternal family (subjects II.
1, II.3, II.5) was found an allele with the R483->frame disturbance mutation, also known as R483delGGinsC, which consists of the change of the nucleotide reading,
Thus, it was stated that the six spouses have mutations for HSC salt-wasting, and therefore are at risk of having daughters with genital ambiguity.
Genetic counseling and management of pregnancies
Genetic counseling is given to the three affected marriages.
The paternal aunt (subject II.2), healthy woman of 34 years, suspends the contraceptive method for desires of fertility and achieves spontaneous conception in March 2005.
The benefits and risks of prenatal treatment with corticosteroids are explained, which the patient understands and accepts, signing a consent in which he chooses to perform this therapy.
Treatment began at 6 weeks of gestational age (GA) with dexamethasone at a dose of 20 μg/kg/day.
At 13 weeks, the diagnosis of male fetus was made by high resolution ultrasonography (Voluson 730, General Electric, Austria, transabdominal transducer 3.5-5 MHz), which was not able to predict prenatal EG6 after 12 weeks gestation.
Steroid doses were progressively reduced and completely suspended at 22 weeks.
During the treatment period the patient developed edema and hypertension that required treatment with amethyldo-pa.
The symptoms partially reverted with the suspension of corticoid therapy, and totally postpartum.
At 39 weeks a cesarean section was performed and a male newborn with adequate weight and normal physical examination was obtained.
The levels of 170HP at 5 days are shown in the Figure.
Maternal aunt (subject II.5) of 37 years consulted for an initial pregnancy of 5 weeks of GA.
A new prenatal treatment of CSH was offered, and an informed consent form was also requested.
The family chose to follow this treatment again.
At 6 weeks of GA dexamethasone was started at a dose of 20 Lig/kg/day.
The mother did not accept the invasive techniques of prenatal diagnosis and it was decided to make a diagnosis of fetal sex by early ultrasound.
If the fetus was a female, treatment continued until the end of pregnancy.
At 12 weeks, male fetus was diagnosed and steroids were suspended.
The patient had no adverse effects to dexamethasone.
At 40 weeks, a healthy, unaffected child was born.
